Herpes Simplex Virus (“HSV”) is a family of viruses that infects a large portion of the human population. HSV occurs in at least two well known varieties, particularly Herpes Simplex Virus 1 (“HSV-1”) and Herpes Simplex Virus 2 (“HSV-2”). It has been estimated that by the age of fifty (50), eighty to ninety (80-90) percent of human beings carry HSV-1 antibodies. It is also estimated that twenty to thirty (20-30) percent of the human population is infected with the HSV-2 virus. Once a person is infected, HSV remains in an inactive state in the body and may cause recurring lesions throughout the life of an infected person. The high prevalence of the human population that carries either HSV-1 or HSV-2 leads to an ever increasing number of persons who experience lesions caused by either HSV virus strain. The viruses often cause lesions on the area surrounding the mouth and/or the genital area of those carrying HSV-1 or HSV-2.
A well known example of a HSV caused lesion is a cold sore or fever blister on or around the month of a person infected with HSV-1 or HSV-2. A cold sore is a lesion consisting of small blisters on the lip or surrounding mouth that lasts from 5 to 14 days. These lesions are caused when vesicles form, break open, and leak a clear fluid. The lesions usually scab over after a few days and heal themselves. While these lesions usually heal themselves in 5 to 14 days, they are unsightly and may be very painful to those experiencing them. Herpes Simplex Virus lesions, other than cold sores, are similar in appearance and duration.
Most over-the-counter topical treatments for cold sores are topical anesthetics to decrease pain, skin protectants (petroleum or zinc oxide), antiseptics, or herbal remedies. Most of these topical treatments attempt to reduce the pain, discomfort and appearance of the cold sore but usually have little effect on the duration of the lesion, in addition, antiviral medications have been developed in an attempt to reduce the occurrence of lesion outbreaks and attempt to subvert the viral activity in the body. Many of these antiviral medications are administered orally. Antiviral medications have also been developed as topical treatments in an attempt to slow down the activity of the virus within the lesion and are usually most effective if administered prior to the formation of the vesicles. Two well known and commercially available antiviral compounds are Penciclovir and Acyclovir.
Penciclovir is generally poorly adsorbed orally; therefore, it is often used more as a topical treatment. Penciclovir is often available by prescription in the pharmaceutical cream DENAVIR® which contains one percent (1%) Penciclovir. Use of 1% Penciclovir cream has been found to reduce the duration of a cold sore by an average of one-half day (an average of 4.5 days treated versus 5.0 days for untreated cold sores). Acyclovir is an antiviral that is administered through oral tablets, topical cream, intravenous injection and ophthalmic cream. A five percent (5%) Acyclovir topical cream is commercially available in the topical medication ZORVIRAX™ cold sore cream. Similar to Penciclovir, 5% Acyclovir cream has also been clinically shown to reduce the duration of a cold sore by an average of one-half day.
There have been other efforts made to improve the performance of these drugs when used to combat herpes viral infections. For example, U.S. Pat. No. 6,469,015 issued to Griffiths, et al., discloses the inclusion of solubilized Penciclovir in a topical formulation comprising propylene glycol. This formulation was developed to increase the absorbance of the drug at the skin and thereby provide and increased effective dosage to the lesion area.
Synergistic combinations of antivirals with other compounds have been reported. For example, U.S. Pat. No. 5,552,384 issued to Deziel, et al., discloses the use of an antiviral nucleoside analog with a ribonucleotide reductase inhibiting peptide derivative. Such a combination was reported to have increased antiviral activity without increased toxicity.
The synergistic effects of combinations of multiple antivirals have also been reported, but without suggesting the compounds disclosed herein. For example, Sutton, et al., “Activity of Penciclovir in Combination with Azido-Thymidine, Ganciclovir, Acyclovir, Foscarnet and Human Interferons against Herpes-Simplex Virus-Replication in Cell-Culture,” Antiviral Chemistry and Chemotherapy, vol. 4, no. 2 pg, 85-94 (1992), discloses the use of Penciclovir with other antivirals including acyclovir. However, the in-vitro studies conducted showed that the combinations of antivirals had affects that were, “purely additive.”
Considering cold sores usually have a duration of 5-14 days, a one-half day reduction in the duration of a cold sore resulting from treatment with antiviral compounds known in the prior art provides little improvement over not implementing any treatment at all. As such, there is a long-felt need in the art to provide a therapeutic compound to reduce the duration and scope of lesions resulting from the Herpes Simplex Virus, One embodiment being, a treatment that will drastically reduce the duration of a cold sore when vesicles have already appeared and a treatment that will prevent the formation of vesicles and a lesion when applied in the prodromal stage.